Page 219 - Haematologica Atlas of Hematologic Cytology

CHAPTER 26 - Inherited hemolytic anemias
DEFECT IN PERMEABILITY OF RED CELL MEMBRANE
The term hereditary stomatocytosis (HSt) refers to to to to to to di di di erent rare diseases due to to to to to to abnormali es es es es of RBC mem- brane permeability to to to to to to monovalent ca ons (Na+ and K+) that result in in altera on on on on in in the erythrocytes water content (Figure C) The clinical manifesta on on can can vary from asymptoma c c c c c c c c to to severe hemoly c c c c c c c c anemia signi cant co-morbidi es es such as
as
iron overload are frequently observed Hereditary stomatocytosis stomatocytosis is is is is divided into two main classes according to to to to to to to to to to increased shrinkage or or swelling of the erythrocytes: dehydrated hereditary hereditary hereditary stomatocytosis stomatocytosis stomatocytosis (DHSt also known as
as
as
as
hereditary hereditary hereditary xerocytosis) due to to to to to to to to to to to to to muta muta ons ons in in in the the the PIEZO1 gene gene gene and overhydrated hereditary hereditary hereditary stomatocytosis stomatocytosis stomatocytosis (OHSt) associated associated with muta muta muta ons ons ons in in in the the the RhAG gene gene gene A A A A new variant of stomatocytosis stomatocytosis has recently been described associated associated to to to to to to to to muta muta ons ons in in in in in in the the the the KCNN4 gene gene gene coding for for Gardos Channel other rarer forms include defects in in in in ABCB6 (pseudohyperkalemia) SLC4A1 (sphero-sto- matocytosis) or or or GLUT1 (cryohydrocytosis with neurological impairment) Number of of typical RBCs known as
stomatocytes (mouth-featured cells) in in in blood blood smear smear examina on varies Sto- matocytes matocytes are also observed in in in in peripheral blood blood smears of of pa ents with the the metabolic disorder sitosterolemia caused by muta ons in in the ABCG5 and ABCG8 genes Figure C C C Molecular basis of of hereditary stomatocytosis Ionic transports and and consequently RBC RBC homeostasis and and cell volume regula regula on on on on on on are maintained through the ac ac on on on on on on of of of of di di di erent erent RBC RBC transmembrane transmembrane proteins proteins regulated by di di di di erent erent erent mechanisms mechanisms of of of of ac ac on on on on on on Upper line: line: Schema c c c c c c c c c c representa on on on on on on of of of of transmembrane transmembrane proteins proteins involved in in in in in in in in in heredi- tary stomatocytosis Lower line: line: Pathogene c c c c c c c c mechanisms mechanisms ionic deregula on on on on in in in in in di di erent erent forms of of of HSt DEFECT IN RED CELL ENZYMES
Red cell enzyme de ciencies can lead to to di erent clinical phenotypes: hemoly hemoly c c c c c c c c c c c c c c c c anemia anemia (acute or or chronic) methemoglobinemia or or or erythrocytosis Chronic non-spherocy c c c c c c c c c c c c c c c c c c c hemoly hemoly c c c c c c c c c c c c c c c c c c c anemia anemia (CNSHA) is is is is generally associated with abnormali es es of of of of enzymes of of of of the the the Embden-Myerhof pathway (glycolysis) and nucleo de de de de metabolism Acute he- molysis is is is is is typically observed in in in in defects of of of of of the the the the pentose phosphate phosphate shunt in in in in par cular in in in in glucose-6-phosphate dehy- drogenase (G6PD) de de de ciency or or or glutathione metabolism with the the the the excep on on on on on of of of the the the the class-I G6PD G6PD which results in in in in in chronic hemolysis and neonatal aundice Conversely abnormali es es es of of of the the the Rapoport-Luebering shunt (bisphospho- glycerate mutase de de de ciency) typically results in in in in erythocytosis whereas defect of of NADH-cytochrome b5 reductase (belonging to to to the the the the nucleo de de de de de metabolism pathway) is is is is is associated with methemoglobinemia The degree of of of hemolysis is is is is variable and and and depends on on the the the the the the the metabolic cycle involved the the the the the the the rela ve ve importance of of of the the the the the the the a a a a a a a a a a a a a a ected enzyme enzyme and and and the the the the the proper es es of of of the the the the the mutant enzyme enzyme with regard to kine c c c c c c abnormali es es and/or instability KCNN4 RhAG GLUT1 Overhydrated stomatocytosis Hereditary Xerocytosis
H2O Out
In Ca2+ ATP
ADP+Pi
K+ Na+ ATP
Ca2+ K+ 3Na+
2K+ ADP+Pi
Gardos Channelopathy
H2O Out
In ATP
H2O K+ 3Na+
Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ ATP
Ca2+ Ca2+ Ca2+ Ca2+ 2K+ ADP+Pi
ADP+Pi
ADP+Pi
Out
K+ K+ K+ K+ K+ K+ K+ K+ K+ 3Na+
ATP
2K+ ADP+Pi
Hereditary Xerocytosis
PIEZO1 Gardos Channellopathy
Overhydrated Cryohydrocytosis Stomatocytosis
Sphero- stomatocytosis SLC4A1 Familial pseudoiperkaliemia
ABCB6 In Na+ Na+ Na+ Na+ H2O 206